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Lipid abnormalities in patients with chronic kidney disease not requiring dialysis

Gerald B Appel, MD
Section Editor
Gary C Curhan, MD, ScD
Deputy Editor
Alice M Sheridan, MD


Abnormalities in lipid metabolism occur in patients with all stages of chronic kidney disease (CKD) [1-7]. The most common dyslipidemia in CKD and dialysis is hypertriglyceridemia, whereas the total cholesterol concentration can be high, normal, or low, perhaps due in part to malnutrition [8]. In contrast, the nephrotic syndrome is typically associated with hypercholesterolemia and hypertriglyceridemia.

This topic will review the pathogenesis, epidemiology, and treatment of lipid abnormalities in CKD. The pathogenesis and significance of lipid abnormalities in nephrotic syndrome and following kidney transplantation, the association between CKD and coronary heart disease (CHD), and the management of lipids in patients with CKD who require dialysis are discussed separately. (See "Lipid abnormalities in nephrotic syndrome" and "Lipid abnormalities after renal transplantation" and "Chronic kidney disease and coronary heart disease" and "Secondary prevention of cardiovascular disease in end-stage renal disease (dialysis)", section on 'Lipid modification'.)


The pathogenesis of most lipid abnormalities in patients with CKD primarily involves defective removal from the circulation. The diminished clearance of triglycerides, which can lead to hypertriglyceridemia, stems both from an alteration in the composition of circulating triglycerides (which become enriched with apolipoprotein C-III) and, perhaps later, from reductions in the activity of lipoprotein lipase and hepatic triglyceride lipase, which are involved in triglyceride removal [3,4,9].

Why lipoprotein lipase activity is reduced in CKD is not well understood, but has been thought to reflect increased inhibitor activity [4]. The associated secondary hyperparathyroidism may play a contributory role, perhaps by increasing calcium accumulation within the cells in the liver and adipose tissue. Studies in humans and experimental animals with CKD suggest that parathyroidectomy can normalize serum triglyceride levels and hepatic lipase activity [10,11]. In experimental animals, benefit can also be achieved with verapamil by a similar mechanism [12], although this has not been confirmed in humans.

Another possible mechanism for hypertriglyceridemia in CKD is retention of a circulating inhibitor of lipoprotein lipase, such as pre-beta-high density lipoprotein (HDL) [13]. Pre-beta-HDL is a form of apolipoprotein A-I found in the non-lipoprotein fraction of normal plasma.


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Literature review current through: May 2016. | This topic last updated: Jun 3, 2015.
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  1. Wheeler DC, Bernard DB. Lipid abnormalities in the nephrotic syndrome: causes, consequences, and treatment. Am J Kidney Dis 1994; 23:331.
  2. Appel G. Lipid abnormalities in renal disease. Kidney Int 1991; 39:169.
  3. Sentí M, Romero R, Pedro-Botet J, et al. Lipoprotein abnormalities in hyperlipidemic and normolipidemic men on hemodialysis with chronic renal failure. Kidney Int 1992; 41:1394.
  4. Attman PO, Samuelsson O, Alaupovic P. Lipoprotein metabolism and renal failure. Am J Kidney Dis 1993; 21:573.
  5. Sechi LA, Zingaro L, De Carli S, et al. Increased serum lipoprotein(a) levels in patients with early renal failure. Ann Intern Med 1998; 129:457.
  6. Afzali B, Haydar AA, Vinen K, Goldsmith DJ. From Finland to fatland: beneficial effects of statins for patients with chronic kidney disease. J Am Soc Nephrol 2004; 15:2161.
  7. Kwan BC, Kronenberg F, Beddhu S, Cheung AK. Lipoprotein metabolism and lipid management in chronic kidney disease. J Am Soc Nephrol 2007; 18:1246.
  8. Weiner DE, Sarnak MJ. Managing dyslipidemia in chronic kidney disease. J Gen Intern Med 2004; 19:1045.
  9. Arnadottir M, Thysell H, Dallongeville J, et al. Evidence that reduced lipoprotein lipase activity is not a primary pathogenetic factor for hypertriglyceridemia in renal failure. Kidney Int 1995; 48:779.
  10. Lacour B, Roullet JB, Liagre AM, et al. Serum lipoprotein disturbances in primary and secondary hyperparathyroidism and effects of parathyroidectomy. Am J Kidney Dis 1986; 8:422.
  11. Liang K, Oveisi F, Vaziri ND. Role of secondary hyperparathyroidism in the genesis of hypertriglyceridemia and VLDL receptor deficiency in chronic renal failure. Kidney Int 1998; 53:626.
  12. Akmal M, Perkins S, Kasim SE, et al. Verapamil prevents chronic renal failure-induced abnormalities in lipid metabolism. Am J Kidney Dis 1993; 22:158.
  13. Cheung AK, Parker CJ, Ren K, Iverius PH. Increased lipase inhibition in uremia: identification of pre-beta-HDL as a major inhibitor in normal and uremic plasma. Kidney Int 1996; 49:1360.
  14. Yamamoto S, Kon V. Mechanisms for increased cardiovascular disease in chronic kidney dysfunction. Curr Opin Nephrol Hypertens 2009; 18:181.
  15. Frischmann ME, Kronenberg F, Trenkwalder E, et al. In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients. Kidney Int 2007; 71:1036.
  16. Seres DS, Strain GW, Hashim SA, et al. Improvement of plasma lipoprotein profiles during high-flux dialysis. J Am Soc Nephrol 1993; 3:1409.
  17. Lo JC, Go AS, Chandra M, et al. GFR, body mass index, and low high-density lipoprotein concentration in adults with and without CKD. Am J Kidney Dis 2007; 50:552.
  18. Muntner P, Hamm LL, Kusek JW, et al. The prevalence of nontraditional risk factors for coronary heart disease in patients with chronic kidney disease. Ann Intern Med 2004; 140:9.
  19. Kuboyama M, Ageta M, Ishihara T, et al. Serum lipoprotein(a) concentration and Apo(a) isoform under the condition of renal dysfunction. J Atheroscler Thromb 2003; 10:283.
  20. Wilson DE, Chan IF, Cheung AK, et al. Retinyl ester retention in chronic renal failure. Further evidence for a defect in chylomicron remnant metabolism. Atherosclerosis 1985; 57:189.
  21. Maggi E, Bellazzi R, Falaschi F, et al. Enhanced LDL oxidation in uremic patients: an additional mechanism for accelerated atherosclerosis? Kidney Int 1994; 45:876.
  22. Liu Y, Coresh J, Eustace JA, et al. Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. JAMA 2004; 291:451.
  23. Kilpatrick RD, McAllister CJ, Kovesdy CP, et al. Association between serum lipids and survival in hemodialysis patients and impact of race. J Am Soc Nephrol 2007; 18:293.
  24. Contreras G, Hu B, Astor BC, et al. Malnutrition-inflammation modifies the relationship of cholesterol with cardiovascular disease. J Am Soc Nephrol 2010; 21:2131.
  25. Iseki K, Yamazato M, Tozawa M, Takishita S. Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients. Kidney Int 2002; 61:1887.
  26. Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int 2003; 63:793.
  27. Kovesdy CP, Anderson JE, Kalantar-Zadeh K. Inverse association between lipid levels and mortality in men with chronic kidney disease who are not yet on dialysis: effects of case mix and the malnutrition-inflammation-cachexia syndrome. J Am Soc Nephrol 2007; 18:304.
  28. Shlipak MG, Fried LF, Cushman M, et al. Cardiovascular mortality risk in chronic kidney disease: comparison of traditional and novel risk factors. JAMA 2005; 293:1737.
  29. Chawla V, Greene T, Beck GJ, et al. Hyperlipidemia and long-term outcomes in nondiabetic chronic kidney disease. Clin J Am Soc Nephrol 2010; 5:1582.
  30. Lowrie EG, Lew NL. Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 1990; 15:458.
  31. Degoulet P, Legrain M, Réach I, et al. Mortality risk factors in patients treated by chronic hemodialysis. Report of the Diaphane collaborative study. Nephron 1982; 31:103.
  32. Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011; 377:2181.
  33. KDIGO Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease. Kidney Int Suppl 2013; 3:263.
  34. Sarnak MJ, Bloom R, Muntner P, et al. KDOQI US commentary on the 2013 KDIGO Clinical Practice Guideline for Lipid Management in CKD. Am J Kidney Dis 2015; 65:354.
  35. Navaneethan SD, Pansini F, Perkovic V, et al. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev 2009; :CD007784.
  36. Shepherd J, Kastelein JJ, Bittner V, et al. Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (Treating to New Targets) study. J Am Coll Cardiol 2008; 51:1448.
  37. Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011; 377:2181.
  38. Upadhyay A, Earley A, Lamont JL, et al. Lipid-lowering therapy in persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med 2012; 157:251.
  39. Palmer SC, Craig JC, Navaneethan SD, et al. Benefits and harms of statin therapy for persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med 2012; 157:263.
  40. Hou W, Lv J, Perkovic V, et al. Effect of statin therapy on cardiovascular and renal outcomes in patients with chronic kidney disease: a systematic review and meta-analysis. Eur Heart J 2013; 34:1807.
  41. Wanner C, Krane V, März W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005; 353:238.
  42. Fellström BC, Jardine AG, Schmieder RE, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009; 360:1395.
  43. Nishizawa Y, Shoji T, Nishitani H, et al. Hypertriglyceridemia and lowered apolipoprotein C-II/C-III ratio in uremia: effect of a fibric acid, clinofibrate. Kidney Int 1993; 44:1352.
  44. Tonelli M, Collins D, Robins S, et al. Gemfibrozil for secondary prevention of cardiovascular events in mild to moderate chronic renal insufficiency. Kidney Int 2004; 66:1123.